TY - JOUR
T1 - Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca2+ homeostasis in cardiomyocytes
AU - Tagashira, Hideaki
AU - Bhuiyan, Md Shenuarin
AU - Shinoda, Yasuharu
AU - Kawahata, Ichiro
AU - Numata, Tomohiro
AU - Fukunaga, Kohji
N1 - Funding Information:
This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (KAKENHI 22K06659 and 244360 to H.T.) and Japan Agency for Medical Research and Development (AMED 22ym0126095h0001 to K.I.). The manuscript was edited by a native English science writer belonging to EIGO EXPERTS PVT. LTD.
Publisher Copyright:
© 2022 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - The Sigma-1 receptor (Sigmar1) is downregulated in heart failure model mice with mitochondrial dysfunction. However, the mechanism in detail has not been investigated. In this study, we investigated the role of Sigmar1 in ER-mitochondria proximity using Sigmar1-knockdown or -overexpressed neonatal rat ventricular myocytes (NRVMs). The endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy was aggravated with the dysregulation of mitochondrial function and ER-mitochondrial junctional formation in Sigmar1-knockdown NRVMs, whereas improved in Sigmar1 overexpressed NRVMs. Our data suggests that the reduction of the cardiac Sigmar1 results in decrease mitochondrial Ca2+ influx and promotes mitochondrial fission, followed by reduced ER-mitochondria proximity, exacerbating ET-1-induced cardiomyocyte injury.
AB - The Sigma-1 receptor (Sigmar1) is downregulated in heart failure model mice with mitochondrial dysfunction. However, the mechanism in detail has not been investigated. In this study, we investigated the role of Sigmar1 in ER-mitochondria proximity using Sigmar1-knockdown or -overexpressed neonatal rat ventricular myocytes (NRVMs). The endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy was aggravated with the dysregulation of mitochondrial function and ER-mitochondrial junctional formation in Sigmar1-knockdown NRVMs, whereas improved in Sigmar1 overexpressed NRVMs. Our data suggests that the reduction of the cardiac Sigmar1 results in decrease mitochondrial Ca2+ influx and promotes mitochondrial fission, followed by reduced ER-mitochondria proximity, exacerbating ET-1-induced cardiomyocyte injury.
KW - Cardiac hypertrophy
KW - Mitochondria
KW - Sigma receptors
UR - http://www.scopus.com/inward/record.url?scp=85146245779&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146245779&partnerID=8YFLogxK
U2 - 10.1016/j.jphs.2022.12.005
DO - 10.1016/j.jphs.2022.12.005
M3 - Article
C2 - 36707178
AN - SCOPUS:85146245779
SN - 1347-8648
VL - 151
SP - 128
EP - 133
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 2
ER -